This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. VEGF Trap is a humanized recombinant fusion protein that binds VEGF with high affinity and has been shown to block VEGF signaling pathways. Animal models have revealed significant anti-tumor activity against several different tumor types prompting successful adult Phase I clinical trials and ongoing Phase II trials. We propose a Phase I dose escalation trial of VEGF Trap in children >1 year and <21 years old with relapsed or refractory solid tumors. In Part A of the study, we will determine the maximum tolerated dose of VEGF Trap and recommended Phase II dose of VEGF Trap when administered once every 14 days. The starting dose will be 2 mg/kg/dose given intravenously once every 14 days. The maximum tolerated dose will be determined based on toxicity during the first 2 cycles (each lasting 14 days), with a maximum dose escalation of 5mg/kg/dose IV every 14 days. After the recommended Phase II dose has been determined for the 14 day schedule, Part B of the study will determine the toxicities associated with administration of VEGF Trap given intravenously every 21 days at 150% of the recommended pediatric Phase II dose of Part A. We will also report the toxicities of VEGF Trap in all patients. Pharmacokinetic studies will be performed during cycle 1 and cycle 2 to determine the trough levels of bound and free VEGF Trap. Monitoring for anti-VEGF Trap antibodies will be performed. Correlative studies will be completed including assay of circulating endothelial cells, placental growth factor, soluble VEGFR1, soluble VEGFR2, and RNA levels of VEGFR1 and VEGFR2 in peripheral blood mononuclear cells. We will also explore changes in tumor vascular permeability in response to VEGF Trap using DCEMRI. Finally, within the confines of a Phase I study, we plan to report the activity profile of VEGF Trap in pediatric solid tumors. I. HYPOTHESIS VEGF Trap will have anti-tumor activity in children with refractory solid tumors. II. SPECIFIC AIMS Primary Aims 1. To estimate the maximum tolerated dose (MTD) or recommended Phase 2 dose of VEGF Trap administered intravenously every 14 days to children with refractory solid tumors. 2. To estimate the maximum tolerated dose (MTD) or recommended Phase 2 dose of VEGF Trap administered intravenously every 21 days to children with refractory solid tumors. 3. To define and describe the toxicities of intravenous VEGF Trap administered on a 14 day and 21 day schedule, respectively. 4. To characterize the pharmacokinetics of intravenous VEGF Trap in children with refractory cancer. Secondary Aims 1. To preliminarily define the antitumor activity of intravenous VEGF Trap in children with refractory solid tumors within the confines of a Phase 1 study. 2. To describe changes in circulating endothelial cells (CECs) and plasma angiogenic factors during treatment with VEGF Trap. 3. To determine the feasibility of obtaining an early MRI and to explore changes in tumor vascular permeability using dynamic contrast-enhanced MRI (DCE-MRI) in patients receiving VEGF Trap.